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A&R: Modulation of the itaconic acid pathway alleviates lupus in mice

 Last Update: 2022-08-16
 Source: Internet
 Author: User

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Background: Itaconic acid , a Kreb cycle-derived immune metabolite, is synthesized by myeloid cells in response to danger signals to control inflammasome activation, type I interferon (IFN) responses, and oxidative stress

Itaconic acid Itaconic acid controls inflammasome activation, type I interferon (IFN) response and oxidative stress in systemic lupus erythematosus (SLE)

Methods: Female New Zealand Black/New Zealand White F1 lupus-susceptible mice were administered 4-octylitaconic acid (4-OI) or vehicle for 4 weeks after clinical onset (30 weeks of age) (10 mice/grou.

4-Octylitaconic acid (4-OI) 4-Octylitaconic acid (4-OI) excipient peak disease activity

Results: Proteinuria, renal immune complex deposition, renal severity and inflammation scores, and anti-RNP autoantibodies were significantly reduced

Significant reduction in splenomegaly reduction in activation markers reduction ⁺inhibition of JAK1 activation

Gene expression analysis of splenocytes showed that compared with the vehicle group, type I interferon and pro-inflammatory cytokine genes were significantly decreased and Treg-related markers were increased

Type I interferons and pro-inflammatory cytokine genes significantly decreased Treg-related markers and increased 4-OI treatment in vitro reduced pro-inflammatory and B cell responses

Conclusions: These results support targeting immunometabolism as a potentially viable approach for the treatment of autoimmune diseases, with 4-OIs playing a beneficial role in alleviating immune dysregulation and organ damage in lupus

4-OI plays a beneficial role in alleviating immune dysregulation and organ damage in lupus 4-OI plays a beneficial role in alleviating immune dysregulation and organ damage in lupus

Source:

Blanco LP, Patino-Martinez E, Nakabo S, et .

Blanco LP, Patino-Martinez E, Nakabo S, et .
Modulation of the itaconate pathway attenuates murine lupus [published online ahead of print, 2022 Jul
Arthritis Rheumat.
2022;e4228 doi:11002/a.
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